Frontal osteitis complicated with bone necrosis is rare.In addition,the condition has various etiologies,such as frontal sinusitis,penetrating head injury,postoperative complications after sinus surgery,and hematogeno...Frontal osteitis complicated with bone necrosis is rare.In addition,the condition has various etiologies,such as frontal sinusitis,penetrating head injury,postoperative complications after sinus surgery,and hematogenous spread from distant sites.In frontal osteitis,early diagnosis is important,and fistulization of pus in the scalp or on the traumatized forehead may raise the suspicion of osteitis in one of the skull bones.The exclusion of osteonecrosis is such cases is an emergency;hence,a magnetic resonance imaging and a computed tomography scan are required in the absence of skull radiography.Early administration of the appropriate treatment in the immediate post-trauma period ensures effective prevention of frontal osteitis;however,the treatment of bone necrosis involves debridement and antibiotic therapy to prevent fatal intracranial complications.This report presents the case of a 16-year-old female patient who experienced sexual and physical assault that resulted in undetected frontal trauma complicated with frontal osteonecrosis.Thorough clinical examination of the patient was performed,and follow-up and multidisciplinary management enabled the social integration of the patient.展开更多
BACKGROUND Tumor necrosis factor-α(TNF-α)has been implicated in the development of diabetes following chronic pancreatitis.However,its role in abnormal glucose metabolism(AGM)after acute pancreatitis(AP)and post-pan...BACKGROUND Tumor necrosis factor-α(TNF-α)has been implicated in the development of diabetes following chronic pancreatitis.However,its role in abnormal glucose metabolism(AGM)after acute pancreatitis(AP)and post-pancreatitis diabetes mellitus remains unclear.AIM To investigate the role of TNF-αin AP-associated AGM and its effects on isletβ-cell apoptosis,focusing on the underlying molecular mechanisms.METHODS Clinical data were collected to assess AGM’s incidence and identify the characteristics in 369 AP patients.In vitro,AP models were established using lipopolysaccharide in 266-6 acinar cells and MIN-6β-cells.Cell proliferation,apoptosis,and protein expression were analyzed using the Cell Counting Kit-8 assay,terminal deoxynucleotidyl transferase dUTP nick-end labeling assay,and western blotting.The TNF-αand insulin concentration in co-culture medium was measured by enzyme-linked immunosorbent assay.In vivo,an AP mouse model was induced using sodium taurocholate,and pancreatic tissues were analyzed through hematoxylin and eosin staining,terminal deoxynucleotidyl transferase dUTP nick-end labeling,and western blotting.TNF-αlevels were assessed by enzyme-linked immunosorbent assay.A TNF-αinhibitor was applied to the AP cell model to reassess apoptosis and protein expression.RESULTS AGM occurred in 40.38%of AP patients.Body mass index,severity grade,recurrence frequency,and lung injury were significantly associated with AGM.AP models in 266-6 and MIN-6 cells showed reducedβ-cell proliferation,insulin secretion,and increased apoptosis,which correlated with inflammation severity.Similar findings ofβ-cell apoptosis were confirmed in the mouse model.TNF-αlevels were significantly elevated in AP models,with higher levels in severe inflammation.Increased Bax and caspase-3 expression and decreased Bcl-2 expression were observed in both in vitro and in vivo models.These changes intensified with increasing inflammation.TNF-αinhibition reduced apoptosis and altered protein expression patterns,decreasing Bax and caspase-3,while increasing Bcl-2 in MIN-6 cells.CONCLUSION TNF-αcontributes toβ-cell apoptosis and AGM in AP through the Bax/Bcl-2/caspase-3 signaling pathway,suggesting TNF-αas a potential therapeutic target for preventing AP-associated AGM.展开更多
BACKGROUND Endoscopic ultrasound-guided drainage using lumen-apposing metal stents(LAMS)has emerged as the first-line approach for managing walled-off necrosis(WON).However,certain patients require escalation to direc...BACKGROUND Endoscopic ultrasound-guided drainage using lumen-apposing metal stents(LAMS)has emerged as the first-line approach for managing walled-off necrosis(WON).However,certain patients require escalation to direct endoscopic necrosectomy,for which the predictive factors have not been completely defined.AIM To determine the predictors of direct endoscopic necrosectomy following LAMS placement in patients with WON and to assess the clinical outcomes and safety.METHODS A retrospective analysis of prospectively collected data from patients with acute pancreatitis who were admitted to the Govind Ballabh Pant Institute of Postgraduate Medical Education in Delhi,India,between January 2020 and October 2023 was conducted.Patients with acute pancreatitis and symptomatic WON who underwent LAMS placement were included in the study.Patients aged<18 years with asymptomatic WON,pseudocysts,postsurgical collections,or a history of percutaneous drainage were excluded.Data were collected using a predesigned form.Clinical details,treatments,interventions,and outcome data were recorded.RESULTS A total of 104 patients with symptomatic pancreatic WON who underwent LAMS placement were included in this study.Of these,36 required endoscopic necrosectomy.Univariate analysis revealed that fever[odds ratio(OR)=4.47,95%confidence interval(CI):1.85-10.79,P=0.00],systemic inflammatory response syndrome(OR=5.85,95%CI:2.03-16.83,P=0.001),pancreatic necrosis>30%(OR=14.6,95%CI:1.87-113.86,P=0.001),WON in the pancreatic head(OR=4.246,95%CI:1.80-10.0,P=0.001),and collection size(OR=1.18,95%CI:1.04-1.34,P=0.009)were the predictors of endoscopic necrosectomy.Subsequently,multivariate analysis indicated that the extent of necrosis was an independent predictor of the requirement for necrosectomy(OR=1.085,95%CI:1.026-1.148,P<0.004).Clinical success was higher in the non-necrosectomy group than in the necrosectomy group(88.2%vs 69.4%).CONCLUSION Early identification of these predictive variables can guide treatment planning for WON and facilitate early necrosectomy,thereby improving the clinical outcomes.展开更多
This study aimed to investigate the mechanism underlying primary bud necrosis(PBN)in grapevines.PBN is a physiological disorder that significantly reduces grape yields.The four varieties,‘Shine Muscat’,‘Summer Blac...This study aimed to investigate the mechanism underlying primary bud necrosis(PBN)in grapevines.PBN is a physiological disorder that significantly reduces grape yields.The four varieties,‘Shine Muscat’,‘Summer Black’,‘Ruby Seedless’,and‘Hutai 8’,were investigated and found to exhibit differences in PBN,which was positively correlated with the speed and extent of inflorescence differentiation.Among them,‘Summer Black’was most susceptible to PBN.Treatment with gibberellin acid 3(GA_(3))notably accelerated and exacerbated PBN in‘Summer Black’,whereas the endogenous gibberellin(GA)inhibitor chlorocholine chloride(CCC)delayed or prevented PBN onset.Histological observations of dormant bud tissues revealed PBN progression in stages,starting with the expansion of cells in the necrosis zone(NZ),followed by cell wall irregularities and collapse,buckling cell layer formation,and subsequent cell separation.In the water control group,NZ mainly occurred in the bud scale layer.However,by the second week after GA_(3) treatment,primary buds visibly elongated,and NZ was formed at multiple locations along the primary buds.Transcriptomic analyses revealed significant regulation of stress-related genes,including reactive oxygen species(ROS)and heat-shock proteins(HSPs),following GA_(3) treatment.Genes related to jasmonic acid(JA)biosynthesis and signaling pathways were upregulated after week 2,whereas CCC treatment led to the downregulation of these genes.Furthermore,genes associated with cations such as calcium,iron,and copper showed significant changes across all transcriptome samples.Genes associated with the degradation of cell membranes and cell walls were upregulated in samples treated with GA_(3) and water control.Overall,these findings suggested that GA_(3) promoted PBN by enhancing JA synthesis and modulating the cell necrosis pathway via JA signaling.This process involved ROS accumulation and activation of cation pathways,leading to endomembrane and cell wall degradation,cell rupture,and,ultimately,PBN development.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a global health concern,representing the second most common cause of malignancy-related mortality in the world.The primary cause of HCC in the United States is chronic infect...BACKGROUND Hepatocellular carcinoma(HCC)is a global health concern,representing the second most common cause of malignancy-related mortality in the world.The primary cause of HCC in the United States is chronic infection with the hepatitis C virus(HCV).Clinical observations have established sex-based differences in HCV infection with the disease progressing more severely and more rapidly in males and postmenopausal females compared to premenopausal females,suggesting that estrogens and their receptors may play an important role in hepatic defenses and development of HCV-mediated HCC.However,the precise mechanism of estrogen protection and their effects on inflammation is poorly understood.AIM To determine whether estrogen receptor(ER)expression is correlated with the expression of tumor necrosis factor-alpha(TNF-α)in males and females with HCV-associated diseases.METHODS The role of ERs in modulating innate immune responses was investigated using human liver tissues with HCV/cirrhosis and HCV/HCC.Messenger RNA(mRNA)and protein(nuclear and cytoplasmic)expression were measured for all markers of interest and compared to normal human liver tissue samples.RESULTS ERβwas reported for the first time to have a greater mRNA expression than ERαin normal liver(P≤0.001).In addition,ERβmRNA expression was found to be decreased in diseased livers(P≤0.05),while TNF-αexpression was increased(P≤0.0001).Upon stratifying by sex within each disease group,ESR1 was found to be negatively correlated with ESR2 in females with HCV/cirrhosis(r=-0.84,P≤0.001),whereas males with HCV/cirrhosis were found to have a significant positive correlation(r=0.57,P≤0.05).ESR2 mRNA expression had a significant positive correlation with TNF-αin both HCV/cirrhosis(r=0.61,P≤0.001)and HCV/HCC patients(r=0.45,P≤0.05).CONCLUSION All together,these findings indicate that changes in ERβand TNF-αexpression are associated with worsening disease,and may be part of the sex-dependent factors in HCC pathogenesis.展开更多
Cantharidin (CTD), a natural compound used to treat multiple tumors in the clinic setting, has been limited due to acute kidney injury (AKI). However, the major cause of AKI and its underlying mechanism remain to be e...Cantharidin (CTD), a natural compound used to treat multiple tumors in the clinic setting, has been limited due to acute kidney injury (AKI). However, the major cause of AKI and its underlying mechanism remain to be elucidated. Serum creatinine (SCr) and blood urea nitrogen (BUN) were detected through pathological evaluation after CTD (1.5 mg/kg) oral gavage in mice in 3 days. Kidney lipidomics based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to investigate lipids disorder after CTD exposure in mice. Then, spatial metabolomics based on matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) was used to detect the kidney spatial distribution of lipids. Integrative analysis was performed to reveal the spatial lipid disorder mechanism and verify key lipids in vitro. The results showed that the levels of SCr and BUN were increased, and tubular necrosis was observed in mouse kidneys, resulting in acute tubular necrosis (ATN) in CTD-induced AKI. Then, lipidomics results revealed that after CTD exposure, 232 differential lipid metabolites and 11 pathways including glycerophospholipid (GP) and sphingolipid (SL) metabolism were disrupted. Spatial metabolomics revealed that 55 spatial differential lipid metabolites and nine metabolic pathways were disturbed. Subsequently, integrative analysis found that GP metabolism was stimulated in the renal cortex and medulla, whereas SL metabolism was inhibited in the renal cortex. Up-regulated lysophosphatidylcholine (LysoPC) (18:2(9Z,12Z)), LysoPC (16:0/0:0), glycerophosphocholine, and down-regulated sphingomyelin (SM) (d18:0/16:0), SM (d18:1/24:0), and SM (d42:1) were key differential lipids. Among them, LysoPC (16:0/0:0) was increased in the CTD group at 1.1196 μg/mL, which aggravated CTD-induced ATN in human kidney-2 (HK-2) cells. LysoPC acyltransferase was inhibited and choline phosphotransferase 1 (CEPT1) was activated after CTD intervention in mice and in HK-2 cells. CTD induces ATN, resulting in AKI, by activating GP metabolism and inhibiting SL metabolism in the renal cortex and medulla, LysoPC (16:0/0:0), LysoPC acyltransferase, and CEPT1 may be the therapeutic targets.展开更多
BACKGROUND The pathogenesis of primary biliary cholangitis(PBC)remains unclear.Ursodeoxycholic acid(UDCA)is the only first-line clinical treatment,but approximately 40%of patients exhibit a poor response.AIM To identi...BACKGROUND The pathogenesis of primary biliary cholangitis(PBC)remains unclear.Ursodeoxycholic acid(UDCA)is the only first-line clinical treatment,but approximately 40%of patients exhibit a poor response.AIM To identify novel biomarkers for PBC to predict the efficacy of UDCA and enhance treatment.METHODS Microarray expression profiling datasets were downloaded from the Gene Expression Omnibus and analyzed to identify differentially expressed genes between PBC patients and healthy controls.Immunohistochemistry was performed to validate key genes in liver tissues of the participants.Logistic regression was employed to evaluate prognostic risk factors,receiver operating characteristic curves were used to assess predictive performance,and correlations between key genes and clinicopathological characteristics were analyzed.RESULTS By bioinformatic analysis,13 genes primarily associated with the progression of PBC were identified,and tumor necrosis factor alpha-induced protein 3(TNFAIP3)was selected for further investigation.Then expression of TNFAIP3 in PBC patients was significantly elevated compared to healthy controls on immunohistochemistry(P<0.0001).Multivariate Cox regression analysis indicated that both TNFAIP3 and fatigue were independent risk factors for response to UDCA in PBC patients(P<0.05).The area under the curve for TNFAIP3 and fatigue were 0.691 and 0.704,respectively,while their combination showed a significantly higher area under the curve of 0.848.The expression of TNFAIP3 was also correlated with age,albumin,total bilirubin,alkaline phosphatase and splenomegaly(P<0.05).CONCLUSION TNFAIP3 and fatigue are independent risk factors for response to UDCA in Chinese patients with PBC.TNFAIP3 may be a potential biomarker or therapeutic target for PBC.These findings offer new insights into the pathogenesis of PBC.展开更多
BACKGROUND Diabetes and its associated microvascular complications,such as nephropathy and retinopathy,significantly impact global health.These complications often begin in the prediabetic stage,emphasizing the import...BACKGROUND Diabetes and its associated microvascular complications,such as nephropathy and retinopathy,significantly impact global health.These complications often begin in the prediabetic stage,emphasizing the importance of early detection and intervention.Inflammatory pathways are key contributors to these conditions,and recent research has identified members of the tumor necrosis factor(TNF)receptor superfamily as potential biomarkers.However,their association with renal and retinal dysfunction in individuals with intermediate hyperglycemia(IH)remains underexplored.The Early Prevention of Diabetes Complications(ePREDICE)trial provides a valuable cohort to investigate these associations and improve risk assessment strategies.AIM To identify inflammatory biomarkers associated with early renal and retinal dysfunction in individuals with IH.Specifically,we evaluate the diagnostic and prognostic potential of TNF receptor superfamily members[TNF receptor 1(TNF-R1),TNF receptor 2(TNF-R2)],T-cell immunoglobulin and mucin domain 3(TIM-3)/HAVCR2,galectin-3,and interleukin-6(IL-6)in detecting kidney dysfunction and retinopathy in this high-risk population.By understanding their roles,we seek to enhance early screening methods and inform personalized intervention strategies.METHODS A cross-sectional analysis of 967 individuals with IH from the ePREDICE trial was conducted.Participants underwent comprehensive anthropometric and biochemical assessments.Key inflammatory biomarkers,including TNF-R1,TNF-R2,TIM-3/HAVCR2,galectin-3,and IL-6,were quantified using immunoassays.Renal function was assessed using estimated glomerular filtration rate(eGFR)and albuminuria,while retinopathy was evaluated through fundoscopic examination.Statistical analyses included adjusted mean comparisons,correlation studies,and receiver operating characteristic curve analysis to assess biomarker diagnostic accuracy.RESULTS TNF-R1,TNF-R2,and TIM-3/HAVCR2 were significantly associated with reduced filtration function(eGFR<60 mL/minute/1.73 m^(2))and albuminuria,with area under the curve(AUC)values between 0.815 and 0.845.TIM-3/HAVCR2 emerged as the strongest predictor of retinopathy(AUC=0.737).Strong correlations(r>0.75)were observed among TNF-R1,TNF-R2,and TIM-3/HAVCR2,suggesting a coordinated role in inflammatory pathways.CONCLUSION Our findings highlight the potential of TNF receptor superfamily members as biomarkers for early-stage renal and retinal complications in individuals with IH.Their integration into clinical screening protocols could facilitate earlier detection,improving patient stratification and personalized management strategies.Further longitudinal studies are necessary to validate their predictive value and potential for guiding therapeutic interventions in IH and early diabetes management.展开更多
BACKGROUND Although acute pancreatitis and walled-off necrosis(WON)are rare complications following aortic surgery,they are serious risk factors for postoperative mortality.Considering the poor general condition of th...BACKGROUND Although acute pancreatitis and walled-off necrosis(WON)are rare complications following aortic surgery,they are serious risk factors for postoperative mortality.Considering the poor general condition of the postoperative patient,more effective and less invasive treatments are favorable.CASE SUMMARY A 67-year-old man was referred to our hospital for the treatment of WON after acute pancreatitis.He had undergone total aortic arch replacement due to aortic arch aneurysm and coronary artery bypass grafting due to angina pectoris 6 weeks prior in another hospital.On the second postoperative day,laboratory data and computed tomography showed that the patient had developed acute pancreatitis.Although conservative management(antibiotics,hydration,etc.)had helped in relieving the symptoms of acute pancreatitis,peripancreatic fluid collection(PFC)persisted,accompanied by duodenal obstruction and vomiting.Contrastenhanced computed tomography showed that the heterogeneous enhancement and fluid collection in the pancreatic body and tail had increased,consistent with walled-off WON.We therefore performed endoscopic ultrasound-guided transluminal drainage for the PFC.As a result,the WON resolved gradually,resulting in improved oral intake.CONCLUSION Acute pancreatitis is a rare gastrointestinal complication following thoracic and thoracoabdominal aortic aneurysm surgery.To the best of our knowledge,this is the first case of WON after aortic arch surgery treated with endoscopic ultrasound-guided transluminal drainage for PFC.展开更多
Background:Infected pancreatic necrosis(IPN)is a highly morbid local complication following necrotizing pancreatitis.Early enteral nutrition has been proven to be effective in preventing IPN.This study aimed to assess...Background:Infected pancreatic necrosis(IPN)is a highly morbid local complication following necrotizing pancreatitis.Early enteral nutrition has been proven to be effective in preventing IPN.This study aimed to assess the association between the trajectory of prealbumin(PAB)during the early phase of acute pancreatitis(AP)and the incidence of IPN and other clinical outcomes.Methods:This retrospective,dual-centered study screened patients with AP admitted to the Center of Acute Pancreatitis,Jinling Hospital and the Affiliated Hospital of Zunyi Medical University from January 2018 to December 2022.The PAB levels during the first week after admission were collected.The primary outcome was the incidence of IPN within 90 days after AP onset.Group-based trajectory modelling was performed to describe the trajectory of PAB levels over time.A Cox proportional hazard model was used to facilitate the interpretation of the time-varying hazard ratio(HR)between PAB and outcomes.Fine-Gray sub-distribution hazard model was adopted for sensitivity analysis.Results:A total of 373 patients were included,of whom 82(22.0%)were diagnosed with IPN within 90 days.The trajectory model assigned 232 patients to the low-level PAB(L-PAB)group and 141 to the high-level PAB(H-PAB)group.The incidence of 90-day IPN in the L-PAB group was significantly higher than that in the H-PAB group(26.7%vs.14.2%,P=0.005).The multivariate Cox regression model showed that a high PAB trajectory was associated with a lower incidence of IPN(HR=0.52,95%CI:0.30-0.89;P=0.017)after adjustment for potential confounders.In the sensitivity analysis,taking death as a com-peting risk,high PAB trajectory remained significantly associated with a lower incidence of IPN in the Fine-Gray model(HR=0.55,95%CI:0.33-0.92;P=0.022).Conclusions:A high PAB trajectory within the first week of AP was significantly associated with a lower incidence of IPN within 90 days after AP onset.Dynamic monitoring of PAB levels in the early phase of AP may play an important role in stratifying patients at high risk of developing IPN.展开更多
Laparoscopic sleeve gastrectomy(LSG),as an effective treatment for morbid obesity and its metabolic complications,exerts its therapeutic effects by significantly reducing body weight and improving metabolic disorders....Laparoscopic sleeve gastrectomy(LSG),as an effective treatment for morbid obesity and its metabolic complications,exerts its therapeutic effects by significantly reducing body weight and improving metabolic disorders.Its core mechanisms involve multi-level regulation of free fatty acid(FFA)metabolism and chronic low-grade inflammatory states(represented by tumor necrosis factor-alpha,TNF-α).This paper systematically reviews the direct impact of LSG on FFA dynamics including lipolysis,tissue uptake,and oxidation,as well as the molecular pathways through which it indirectly regulates TNF-αby reducing adipose tissue inflammation,improving intestinal barrier function,and modulating epigenetic modifications such as SCD gene methylation.Postoperatively,FFA and TNF-αform a bidirectional promoting feedback loop.LSG effectively breaks this vicious cycle of mutual promotion between the two under obese conditions by reducing FFA levels and inhibiting TNF-αexpression.Lower FFA levels alleviate inflammatory signal activation,while reduced TNF-αinhibits lipolysis,collectively promoting the restoration of insulin sensitivity.A thorough understanding of these mechanisms provides a theoretical basis for optimizing surgical strategies and developing targeted therapies.展开更多
In this article,the author comment on the article by Zang et al.Tumor necrosis factor alpha-induced protein 3(TNFAIP3)was examined in this study as a novel biomarker to predict the efficiency of ursodeoxycholic acid(U...In this article,the author comment on the article by Zang et al.Tumor necrosis factor alpha-induced protein 3(TNFAIP3)was examined in this study as a novel biomarker to predict the efficiency of ursodeoxycholic acid(UDCA)and thereby improved primary biliary cholangitis(PBC)treatment.Differentially expressed genes in PBC patients and healthy controls(HCs)were detected using microarray expression analysis.PBC patients and HCs were examined for predictive performance and associations between important genes and clinicopathological features using immunohistochemistry,logistic regression,and receiver operating characteristic curve methods.Thirteen genes linked to the development of PBC were detected by the bioinformatic research.TNFAIP3 was chosen for additional examination from these 13 genes.TNFAIP3 was shown to be more expressed in PBCs patients than in HCs using immunohistochemical method.TNFAIP3 and fatigue have a significant impact on UDCA in PBC patients in multivariate cox regression analysis.Additionally,there was a correlation between TNFAIP3 expression and splenomegaly,alkaline phosphatase,albumin,total bilirubin,and age.In conclusion,TNFAIP3 and fatigue have significant impact on UDCA in PBC.These findings provide a new view on PBC pathophysiology and suggest that TNFAIP3 may be a suitable biomarker or therapeutic target for the disease.展开更多
BACKGROUND Anti-drug antibodies(ADAs)can reduce the effectiveness of biologics.While human leukocyte antigen(HLA)-DQA1*05 allele is linked to ADA formation in European Crohn’s disease patients,its relevance in non-Eu...BACKGROUND Anti-drug antibodies(ADAs)can reduce the effectiveness of biologics.While human leukocyte antigen(HLA)-DQA1*05 allele is linked to ADA formation in European Crohn’s disease patients,its relevance in non-European populations remains unclear.AIM To investigate HLA genotypes associated with the development of ADAs in Taiwan Region of China inflammatory bowel disease(IBD)patients treated with biologics.METHODS In this multicenter study,IBD patients treated with anti-tumor necrosis factor(TNF),anti-integrin,or anti-interleukin(IL)-12/23 therapies from April 2022 to June 2024 were enrolled.All participants underwent next-generation sequencing for HLA genotyping.ADA levels were measured via enzyme linked immunosorbent assay.HLA allele frequencies were compared between ADA-positive and ADA-negative groups,and against general Taiwan Region of China population data.RESULTS Ninety-five IBD patients were included:58 received anti-TNF therapy(38 infliximab,20 adalimumab),27 antiintegrin,and 10 anti-IL-12/23.ADAs occurred only in the anti-TNF group(n=22):19 infliximab(50%)and 3 adalimumab(15%).No ADAs developed in patients on anti-integrin or anti-IL-12/23 agents.HLA-C*03:04:01 was significantly associated with anti-infliximab ADAs(31.6%vs 0%,P=0.02),and HLA-B*15:18:01 with anti-adalimumab ADAs(66.7%vs 0%,P=0.016).HLA-DQA1*05 was not associated with ADA formation.Frequencies of HLA-C*03:04:01(8.4%vs 10.5%)and HLA-B*15:18:01(1.6%vs 0.6%)in IBD patients were comparable to those in the general population.ADA titers were inversely correlated with serum drug levels.CONCLUSION In Taiwan Region of China IBD patients,HLA-C*03:04:01 and HLA-B*15:18:01 were significantly associated with ADA development to infliximab and adalimumab,respectively.HLA-DQA1*05 was not predictive,highlighting ethnic differences in genetic predisposition to immunogenicity.展开更多
BACKGROUND Irreversible transmural intestinal necrosis(ITIN)is associated with high mortality rates in patients with acute occlusive mesenteric ischemia(AOMI).Currently,there are not many studies on the use of dual en...BACKGROUND Irreversible transmural intestinal necrosis(ITIN)is associated with high mortality rates in patients with acute occlusive mesenteric ischemia(AOMI).Currently,there are not many studies on the use of dual energy computed tomography(DECT)for evaluating ITIN.AIM To evaluate the diagnostic value of DECT for ITIN in AOMI.METHODS The cases and computed tomography(CT)images of 102 patients with clinically diagnosed AOMI(including 48 ITIN)from January 2012 to January 2022 were retrospectively collected.The CT scans included both multidetector CT and DECT.The raw data from DECT portal-venous phase were reconstructed into 120 kVp mixed energy image,50 keV virtual monoenergetic imaging,and iodine map.Two radiologists independently completed the subjective visual assessment of CT signs related to AOMI.Objective parameters,including the attenuation of the normal and_(lesion)intestinal wall segment(CT50 keV_(lesion),CT_(50 keV normal/lesion))and iodine concentrations(IC_(lesion)and I_(Cnormal/lesion)),were quantified.Furthermore,multivariate logistic regression,receiver operating characteristic curves,and area under the curve(AUC)values were used to evaluate the subjective and objective indicators in predicting ITIN.RESULTS Regarding subjective signs,logistic regression analysis revealed reduced or absent bowel wall enhancement[odds ratio(OR)=5.576,95%confidence interval(CI):1.547-20.093],bowel dilation(OR=11.613,95%CI:3.790-35.586),and parenchymatous organ infarction(OR=4.727,95%CI:1.536-14.551)were independent risk factors for the ITIN.CT subjective signs had a high diagnostic efficacy for ITIN(AUC=0.853).The two DECT objective parameters also exhibited excellent diagnostic value for ITIN,with an AUC of 0.79,a cut-off value of CT50 keV normal/_(lesion)=2.81,and an AUC of 0.777 with a cut-off value of I_(Cnormal/lesion)=2.39.The Delong test showed that there was no significant difference in the efficacy of subjective CT signs and objective DECT parameters(P>0.05).Importantly,we observed that I_(Cnormal/lesion)combined with subjective signs(bowel dilation and parenchymatous organ infarction)had the highest predictive performance(AUC=0.894),sensitivity(100%),and specificity(70.83%),which was statistically different from the AUC of CT subjective signs(P=0.017).CONCLUSION I_(Cnormal/lesion)(DECT-based features)combined with CT subjective signs(bowel dilatation and parenchymatous organ infarction)showed favorable predictive performance for ITIN in AOMI,which may help clinicians develop timely treatment strategies.展开更多
BACKGROUND Steroid-induced avascular necrosis of the femoral head(SANFH)involves bone metabolism imbalance and lacks effective therapies.Mesenchymal stem cells(MSCs),particularly human umbilical cord MSCs(hUCMSCs),off...BACKGROUND Steroid-induced avascular necrosis of the femoral head(SANFH)involves bone metabolism imbalance and lacks effective therapies.Mesenchymal stem cells(MSCs),particularly human umbilical cord MSCs(hUCMSCs),offer promise due to their osteogenic and immunomodulatory potential.Sclerostin(SOST)inhibits bone formation,so we developed a multi-target gene silencing strategy against SOST using RNA interference.We created hUCMSCs with SOST-silenced(sh-hUCMSCs)and compared their therapeutic efficacy with unmodified hUCMSCs in SANFH mice.This study explores a novel approach to enhance osteogenesis and mitigate SANFH progression.AIM To assess the effects of sh-hUCMSCs on bone metabolism in SANFH.METHODS hUCMSCs were isolated from placental tissue and transfected with SOST-targeting short hairpin RNA plasmids.A SANFH mouse model was established through intraperitoneal injection of lipopolysaccharide(20μg/kg)followed by intramuscular methylprednisolone administration(40 mg/kg).Mice were randomized into four experimental groups(n=10/group):Sham control,SANFH(untreated),hUCMSCs-treated,and sh-hUCMSCs-treated.Micro-computed tomography was used to measure bone volume(BV),bone surface area,bone surface/BV ratio,tra-becular number,trabecular thickness,and trabecular separation.Quantification of adipocyte area by hematoxylin and eosin staining.Collagen fiber volume was assessed by Masson’s trichrome staining.Serum levels of osteopro-tegerin(OPG),receptor activator of nuclear factor kappa B(RANK),RANK ligand(RANKL),tartrate-resistant acid phosphatase,and the OPG/RANKL ratio were measured by enzyme-linked immunosorbent assay.The expression levels of alkaline phosphatase,OPG,SOST,β-catenin,peroxisome proliferator-activated receptor gamma,and CCAAT/enhancer-binding protein in bone tissue were determined by western blot analysis.RESULTS hUCMSCs and sh-hUCMSCs exhibited typical fibroblast-like morphology and high expression of MSC surface markers(CD90,CD73,CD105>98%).These cells demonstrated tri-lineage differentiation potential,confirmed by positive Alizarin Red S,Oil Red O,and Alcian Blue staining,and upregulation of lineage-specific genes.After SOST-RNA interference modification,sh-hUCMSCs showed enhanced inhibition of adipogenesis and improved bone formation in a rat model of SANFH.Histological analysis revealed reduced lipid infiltration and empty lacunae in the femoral head of the sh-hUCMSC group.Western blot showed decreased CCAAT/enhancer-binding protein and peroxisome proliferator-activated receptor gamma expression(P<0.05).Masson staining and micro-computed tomography analysis confirmed significantly increased BV,trabecular number,trabecular thickness,and reduced trabecular separation in the sh-hUCMSC group compared to unmodified MSCs and SANFH groups(P<0.05).Serum enzyme-linked immunosorbent assay showed higher OPG and lower RANK,RANKL,and tartrate-resistant acid phosphatase levels in the sh-hUCMSCs group.Western blot further confirmed upregulated alkaline phosphatase,OPG,β-catenin,and downregulated SOST expression in sh-hUCMSCs compared to controls(P<0.05).These results suggest that SOST inhibition enhances the osteogenic potential and therapeutic efficacy of hUCMSCs in SANFH.CONCLUSION sh-hUCMSCs alleviate SANFH by activating the Wnt/β-catenin signaling pathway,thereby promoting osteogenic differentiation and suppressing adipogenesis to restore bone metabolic balance.展开更多
Mass mortality of mandarin fish(Siniperca chuatsi)due to infectious spleen and kidney necrosis virus(ISKNV)infection occurs frequently.Since there are no effective drug treatments available,prevention relies heavily o...Mass mortality of mandarin fish(Siniperca chuatsi)due to infectious spleen and kidney necrosis virus(ISKNV)infection occurs frequently.Since there are no effective drug treatments available,prevention relies heavily on detection.Effective and rapid on-site detection methods are needed for early diagnosis of ISKNV.In this study,a rapid and simple colloidal gold test strip method,specific for the antibody against major capsid protein(MCP),was developed and systematically evaluated for the detection of ISKNV.The limit of detection of the test strip is a 1꞉100 dilution of a positive standard serum and the antibody level in the fish could be estimated from the depth of color of the test line.The strips were tested against serum samples of cyprinid herpesvirus-2(CyHV-2),grass carp reovirus(GCRV),largemouth bass ranavirus(LMBV),large yellow croaker iridovirus(LYCIV),and spring viremia of carp virus(SVCV),yielding no cross-reactivity.In addition,10 mandarin fish artificially infected with ISKNV were tested using the current industry standard PCR method(SC/T 7211-2011)on their splenorenal tissues.The results from the test strips showed a high degree of concordance with PCR testing,achieving a Kappa value of 0.737.All the results indicated that the colloidal gold test strips prepared in this study could be used as a simple,rapid,and highly sensitive and specific method for ISKNV diagnosis.展开更多
BACKGROUND Hepatic ischemia reperfusion(HIR)injury is a major complication affecting various major liver surgeries,including liver transplantation.Aprepitant(APRE),a neurokinin-1 receptor antagonist,is commonly used a...BACKGROUND Hepatic ischemia reperfusion(HIR)injury is a major complication affecting various major liver surgeries,including liver transplantation.Aprepitant(APRE),a neurokinin-1 receptor antagonist,is commonly used as an antiemetic to prevent chemotherapy-induced nausea and vomiting.AIM To assess the potential protective effect of APRE against HIR-induced liver injury via targeting the nucleotide-binding oligomerization domain-,leucine-rich repeat-,and pyrin domain-containing receptor 3/interleukin(IL)-1beta signaling pathway.METHODS Six groups of adult male Wistar albino rats were divided as follows:Sham group,Sham/APRE10 group(APRE 10 mg/kg),HIR group,HIR/APRE5 group(APRE 5 mg/kg),HIR/APRE10 group(APRE 10 mg/kg),and HIR/APRE20 group(APRE 20 mg/kg).Serum alanine transaminase,aspartate transaminase,liver malondialdehyde,total antioxidant capacity levels,as well as IL-6,sirtuin 1(Sirt1),caspase-3,cleaved caspase-3,and tumor necrosis factor alpha biomarkers,were evaluated.Hepatic specimens were examined histopathologically and immunohistochemically for nuclear factor erythroid-2-related factor 2(Nrf2)immunoexpression.RESULTS HIR resulted in hepatic damage,as evidenced by histopathological changes and a significant increase in serum alanine transaminase,aspartate transaminase,hepatic malondialdehyde,caspase-3,and tumor necrosis factor alpha levels.Additionally,there were significant increases in hepatic total antioxidant capacity and reductions in IL-6 and cleaved caspase-3 protein levels,as demonstrated by Western blot analysis,along with enhanced immunoexpression of Sirt1 and Nrf2.APRE has significantly reduced various parameters of oxidative stress,inflammation,and apoptosis,and a significant increase in liver Nrf2 immunoexpression,leading to a significant improvement in the histopathological changes.CONCLUSION In conclusion,targeting the Sirt1/Nrf2 signaling pathway,as demonstrated by APRE in our model,could present a promising therapeutic target to protect against HIR-induced liver injury during major liver surgeries.展开更多
The study aimed to explore the efficacy and potential mechanisms of a naturally aromatic cyanogenic compound amygdalin(AMY)in treating glucocorticoid(GC)-associated necrosis of the femoral head(GANFH).We demonstrated ...The study aimed to explore the efficacy and potential mechanisms of a naturally aromatic cyanogenic compound amygdalin(AMY)in treating glucocorticoid(GC)-associated necrosis of the femoral head(GANFH).We demonstrated that GC exacerbates the oxidative stress(OS)microenvironment via promoting nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)expression in human,rat,and mesenchymal stem cells(MSCs)samples,thus generating excessive reactive oxygen species(ROS),leading to increased apoptosis and unbalanced osteolipogenic differentiation.Furthermore,computational docking results revealed that AMY could bind specifically to the predicted binding sites of NOX4.Additionally,AMY ameliorated the OS microenvironment of MSCs via decreasing NOX4 expression and inhibiting NOX4/ROS/p38MAPK signaling,thereby reversing the GC-induced apoptosis and imbalanced osteolipogenic differentiation,and ultimately alleviating GANFH.In summary,we demonstrated for the first time that AMY attenuated apoptosis and maintained osteolipogenic differentiation balance in MSCs via specifically targeting NOX4,inhibiting NOX4/ROS/p38MAPK signaling,thereby treating GANFH.展开更多
Objective:To analyze the value of prophylactic antibiotic use in reducing the incidence of pancreatic necrosis in patients with emergency acute pancreatitis(AP).Methods:A total of 70 AP patients who sought medical att...Objective:To analyze the value of prophylactic antibiotic use in reducing the incidence of pancreatic necrosis in patients with emergency acute pancreatitis(AP).Methods:A total of 70 AP patients who sought medical attention from January 2024 to January 2025 were randomly divided into groups by drawing lots.Group A received prophylactic antibiotic intervention,while Group B received conventional intervention.Results:Group A demonstrated superior outcomes compared to Group B in terms of therapeutic efficacy,duration of symptoms,inflammatory factors,symptom scores,and complication rates,with p<0.05.Conclusion:Prophylactic antibiotic treatment in emergency AP patients leads to a decrease in inflammatory factor levels,alleviation of symptoms,a reduction in the incidence of infectious pancreatic necrosis,and is safe and effective.展开更多
Ulcerative colitis(UC)and Crohn’s disease(CD)are part of Inflammatory Bowel Diseases(IBD)and have pathophysiological processes such as bowel necrosis and enteric neurons and enteric glial cells.In addition,the main i...Ulcerative colitis(UC)and Crohn’s disease(CD)are part of Inflammatory Bowel Diseases(IBD)and have pathophysiological processes such as bowel necrosis and enteric neurons and enteric glial cells.In addition,the main inflammatory mediator is related to the tumor necrosis factor-alpha(TNF-α).TNF-αis a mediator of the intestinal inflammatory processes,thus being one of the main cytokines involved in the pathogenesis of IBD,however,its levels,when measured,are present in the serum of patients with IBD.In addition,TNF-αplays an important role in promoting inflammation,such as the production of interleukins(IL),for instance IL-1βand IL-6.There are two receptors for TNF as following:The tumor necrosis factor 1 receptor(TNFR1);and the tumor necrosis factor 2 receptor(TNFR2).They are involved in the pathogenesis of IBD and their receptors have been detected in IBD and their expression is correlated with disease activity.The soluble TNF form binds to the TNFR1 receptor with,and its activation results in a signaling cascade effects such as apoptosis,cell proliferation and cytokine secretion.In contrast,the transmembrane TNF form can bind both to TNFR1 and TNFR2.Recent studies have suggested that TNF-αis one of the main pro-inflammatory cytokines involved in the pathogenesis of IBD,since TNF levels are present in the serum of both patients with UC and CD.Intravenous and subcutaneous biologics targeting TNF-αhave revolutionized the treatment of IBD,thus becoming the best available agents to induce and maintain IBD remission.The application of antibodies aimed at neutralizing TNF-αin patients with IBD that induce a satisfactory clinical response in up to 60%of patients,and also induced long-term maintenance of disease remission in most patients.It has been suggested that anti-TNF-αagents inactivate the pro-inflammatory cytokine TNF-αby direct neutralization,i.e.,resulting in suppression of inflammation.However,anti-TNF-αantibodies perform more complex functions than a simple blockade.展开更多
文摘Frontal osteitis complicated with bone necrosis is rare.In addition,the condition has various etiologies,such as frontal sinusitis,penetrating head injury,postoperative complications after sinus surgery,and hematogenous spread from distant sites.In frontal osteitis,early diagnosis is important,and fistulization of pus in the scalp or on the traumatized forehead may raise the suspicion of osteitis in one of the skull bones.The exclusion of osteonecrosis is such cases is an emergency;hence,a magnetic resonance imaging and a computed tomography scan are required in the absence of skull radiography.Early administration of the appropriate treatment in the immediate post-trauma period ensures effective prevention of frontal osteitis;however,the treatment of bone necrosis involves debridement and antibiotic therapy to prevent fatal intracranial complications.This report presents the case of a 16-year-old female patient who experienced sexual and physical assault that resulted in undetected frontal trauma complicated with frontal osteonecrosis.Thorough clinical examination of the patient was performed,and follow-up and multidisciplinary management enabled the social integration of the patient.
基金Supported by Taicang Science and Technology Program,No.TC2021JCYL21“National Tutor System”Training Program for Health Youth Key Talents in Suzhou,No.Qngg2023042Suzhou Science and Technology Bureau,No.SYW2024152.
文摘BACKGROUND Tumor necrosis factor-α(TNF-α)has been implicated in the development of diabetes following chronic pancreatitis.However,its role in abnormal glucose metabolism(AGM)after acute pancreatitis(AP)and post-pancreatitis diabetes mellitus remains unclear.AIM To investigate the role of TNF-αin AP-associated AGM and its effects on isletβ-cell apoptosis,focusing on the underlying molecular mechanisms.METHODS Clinical data were collected to assess AGM’s incidence and identify the characteristics in 369 AP patients.In vitro,AP models were established using lipopolysaccharide in 266-6 acinar cells and MIN-6β-cells.Cell proliferation,apoptosis,and protein expression were analyzed using the Cell Counting Kit-8 assay,terminal deoxynucleotidyl transferase dUTP nick-end labeling assay,and western blotting.The TNF-αand insulin concentration in co-culture medium was measured by enzyme-linked immunosorbent assay.In vivo,an AP mouse model was induced using sodium taurocholate,and pancreatic tissues were analyzed through hematoxylin and eosin staining,terminal deoxynucleotidyl transferase dUTP nick-end labeling,and western blotting.TNF-αlevels were assessed by enzyme-linked immunosorbent assay.A TNF-αinhibitor was applied to the AP cell model to reassess apoptosis and protein expression.RESULTS AGM occurred in 40.38%of AP patients.Body mass index,severity grade,recurrence frequency,and lung injury were significantly associated with AGM.AP models in 266-6 and MIN-6 cells showed reducedβ-cell proliferation,insulin secretion,and increased apoptosis,which correlated with inflammation severity.Similar findings ofβ-cell apoptosis were confirmed in the mouse model.TNF-αlevels were significantly elevated in AP models,with higher levels in severe inflammation.Increased Bax and caspase-3 expression and decreased Bcl-2 expression were observed in both in vitro and in vivo models.These changes intensified with increasing inflammation.TNF-αinhibition reduced apoptosis and altered protein expression patterns,decreasing Bax and caspase-3,while increasing Bcl-2 in MIN-6 cells.CONCLUSION TNF-αcontributes toβ-cell apoptosis and AGM in AP through the Bax/Bcl-2/caspase-3 signaling pathway,suggesting TNF-αas a potential therapeutic target for preventing AP-associated AGM.
文摘BACKGROUND Endoscopic ultrasound-guided drainage using lumen-apposing metal stents(LAMS)has emerged as the first-line approach for managing walled-off necrosis(WON).However,certain patients require escalation to direct endoscopic necrosectomy,for which the predictive factors have not been completely defined.AIM To determine the predictors of direct endoscopic necrosectomy following LAMS placement in patients with WON and to assess the clinical outcomes and safety.METHODS A retrospective analysis of prospectively collected data from patients with acute pancreatitis who were admitted to the Govind Ballabh Pant Institute of Postgraduate Medical Education in Delhi,India,between January 2020 and October 2023 was conducted.Patients with acute pancreatitis and symptomatic WON who underwent LAMS placement were included in the study.Patients aged<18 years with asymptomatic WON,pseudocysts,postsurgical collections,or a history of percutaneous drainage were excluded.Data were collected using a predesigned form.Clinical details,treatments,interventions,and outcome data were recorded.RESULTS A total of 104 patients with symptomatic pancreatic WON who underwent LAMS placement were included in this study.Of these,36 required endoscopic necrosectomy.Univariate analysis revealed that fever[odds ratio(OR)=4.47,95%confidence interval(CI):1.85-10.79,P=0.00],systemic inflammatory response syndrome(OR=5.85,95%CI:2.03-16.83,P=0.001),pancreatic necrosis>30%(OR=14.6,95%CI:1.87-113.86,P=0.001),WON in the pancreatic head(OR=4.246,95%CI:1.80-10.0,P=0.001),and collection size(OR=1.18,95%CI:1.04-1.34,P=0.009)were the predictors of endoscopic necrosectomy.Subsequently,multivariate analysis indicated that the extent of necrosis was an independent predictor of the requirement for necrosectomy(OR=1.085,95%CI:1.026-1.148,P<0.004).Clinical success was higher in the non-necrosectomy group than in the necrosectomy group(88.2%vs 69.4%).CONCLUSION Early identification of these predictive variables can guide treatment planning for WON and facilitate early necrosectomy,thereby improving the clinical outcomes.
基金supported by National Technology System for Grape Industry(Grant No.CARS-29-zp-9)National Key Research and Development Program of China(Grant No.2021YFD1200200)Natural Science Foundation of Hunan Province of China(Grant No.2023JJ50063).
文摘This study aimed to investigate the mechanism underlying primary bud necrosis(PBN)in grapevines.PBN is a physiological disorder that significantly reduces grape yields.The four varieties,‘Shine Muscat’,‘Summer Black’,‘Ruby Seedless’,and‘Hutai 8’,were investigated and found to exhibit differences in PBN,which was positively correlated with the speed and extent of inflorescence differentiation.Among them,‘Summer Black’was most susceptible to PBN.Treatment with gibberellin acid 3(GA_(3))notably accelerated and exacerbated PBN in‘Summer Black’,whereas the endogenous gibberellin(GA)inhibitor chlorocholine chloride(CCC)delayed or prevented PBN onset.Histological observations of dormant bud tissues revealed PBN progression in stages,starting with the expansion of cells in the necrosis zone(NZ),followed by cell wall irregularities and collapse,buckling cell layer formation,and subsequent cell separation.In the water control group,NZ mainly occurred in the bud scale layer.However,by the second week after GA_(3) treatment,primary buds visibly elongated,and NZ was formed at multiple locations along the primary buds.Transcriptomic analyses revealed significant regulation of stress-related genes,including reactive oxygen species(ROS)and heat-shock proteins(HSPs),following GA_(3) treatment.Genes related to jasmonic acid(JA)biosynthesis and signaling pathways were upregulated after week 2,whereas CCC treatment led to the downregulation of these genes.Furthermore,genes associated with cations such as calcium,iron,and copper showed significant changes across all transcriptome samples.Genes associated with the degradation of cell membranes and cell walls were upregulated in samples treated with GA_(3) and water control.Overall,these findings suggested that GA_(3) promoted PBN by enhancing JA synthesis and modulating the cell necrosis pathway via JA signaling.This process involved ROS accumulation and activation of cation pathways,leading to endomembrane and cell wall degradation,cell rupture,and,ultimately,PBN development.
基金Supported by Cancer Sucks,Bixby,Oklahoma Research Grant.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a global health concern,representing the second most common cause of malignancy-related mortality in the world.The primary cause of HCC in the United States is chronic infection with the hepatitis C virus(HCV).Clinical observations have established sex-based differences in HCV infection with the disease progressing more severely and more rapidly in males and postmenopausal females compared to premenopausal females,suggesting that estrogens and their receptors may play an important role in hepatic defenses and development of HCV-mediated HCC.However,the precise mechanism of estrogen protection and their effects on inflammation is poorly understood.AIM To determine whether estrogen receptor(ER)expression is correlated with the expression of tumor necrosis factor-alpha(TNF-α)in males and females with HCV-associated diseases.METHODS The role of ERs in modulating innate immune responses was investigated using human liver tissues with HCV/cirrhosis and HCV/HCC.Messenger RNA(mRNA)and protein(nuclear and cytoplasmic)expression were measured for all markers of interest and compared to normal human liver tissue samples.RESULTS ERβwas reported for the first time to have a greater mRNA expression than ERαin normal liver(P≤0.001).In addition,ERβmRNA expression was found to be decreased in diseased livers(P≤0.05),while TNF-αexpression was increased(P≤0.0001).Upon stratifying by sex within each disease group,ESR1 was found to be negatively correlated with ESR2 in females with HCV/cirrhosis(r=-0.84,P≤0.001),whereas males with HCV/cirrhosis were found to have a significant positive correlation(r=0.57,P≤0.05).ESR2 mRNA expression had a significant positive correlation with TNF-αin both HCV/cirrhosis(r=0.61,P≤0.001)and HCV/HCC patients(r=0.45,P≤0.05).CONCLUSION All together,these findings indicate that changes in ERβand TNF-αexpression are associated with worsening disease,and may be part of the sex-dependent factors in HCC pathogenesis.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82260812 and 81803838)the Guizhou Provincial Science&Technology Program,China(Project Nos.:YQK[2023]038 and[2020]5007)+1 种基金the Beijing Natural Science Foundation,China(Grant No.:7254489)the Science and Technology Program of Zunyi city of Guizhou province of China(Project Nos.:(2022)420,[2021]-3,[2020]7,and(2022)419).
文摘Cantharidin (CTD), a natural compound used to treat multiple tumors in the clinic setting, has been limited due to acute kidney injury (AKI). However, the major cause of AKI and its underlying mechanism remain to be elucidated. Serum creatinine (SCr) and blood urea nitrogen (BUN) were detected through pathological evaluation after CTD (1.5 mg/kg) oral gavage in mice in 3 days. Kidney lipidomics based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to investigate lipids disorder after CTD exposure in mice. Then, spatial metabolomics based on matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) was used to detect the kidney spatial distribution of lipids. Integrative analysis was performed to reveal the spatial lipid disorder mechanism and verify key lipids in vitro. The results showed that the levels of SCr and BUN were increased, and tubular necrosis was observed in mouse kidneys, resulting in acute tubular necrosis (ATN) in CTD-induced AKI. Then, lipidomics results revealed that after CTD exposure, 232 differential lipid metabolites and 11 pathways including glycerophospholipid (GP) and sphingolipid (SL) metabolism were disrupted. Spatial metabolomics revealed that 55 spatial differential lipid metabolites and nine metabolic pathways were disturbed. Subsequently, integrative analysis found that GP metabolism was stimulated in the renal cortex and medulla, whereas SL metabolism was inhibited in the renal cortex. Up-regulated lysophosphatidylcholine (LysoPC) (18:2(9Z,12Z)), LysoPC (16:0/0:0), glycerophosphocholine, and down-regulated sphingomyelin (SM) (d18:0/16:0), SM (d18:1/24:0), and SM (d42:1) were key differential lipids. Among them, LysoPC (16:0/0:0) was increased in the CTD group at 1.1196 μg/mL, which aggravated CTD-induced ATN in human kidney-2 (HK-2) cells. LysoPC acyltransferase was inhibited and choline phosphotransferase 1 (CEPT1) was activated after CTD intervention in mice and in HK-2 cells. CTD induces ATN, resulting in AKI, by activating GP metabolism and inhibiting SL metabolism in the renal cortex and medulla, LysoPC (16:0/0:0), LysoPC acyltransferase, and CEPT1 may be the therapeutic targets.
基金Supported by the National Natural Science Foundation of China,No.81671600 and No.81241094Natural Science Foundation of Shandong Province,China,No.ZR2016HM13 and No.ZR2023MH066Qingdao Medical and Health Scientific Research Project,China,No.2024-WJKY160.
文摘BACKGROUND The pathogenesis of primary biliary cholangitis(PBC)remains unclear.Ursodeoxycholic acid(UDCA)is the only first-line clinical treatment,but approximately 40%of patients exhibit a poor response.AIM To identify novel biomarkers for PBC to predict the efficacy of UDCA and enhance treatment.METHODS Microarray expression profiling datasets were downloaded from the Gene Expression Omnibus and analyzed to identify differentially expressed genes between PBC patients and healthy controls.Immunohistochemistry was performed to validate key genes in liver tissues of the participants.Logistic regression was employed to evaluate prognostic risk factors,receiver operating characteristic curves were used to assess predictive performance,and correlations between key genes and clinicopathological characteristics were analyzed.RESULTS By bioinformatic analysis,13 genes primarily associated with the progression of PBC were identified,and tumor necrosis factor alpha-induced protein 3(TNFAIP3)was selected for further investigation.Then expression of TNFAIP3 in PBC patients was significantly elevated compared to healthy controls on immunohistochemistry(P<0.0001).Multivariate Cox regression analysis indicated that both TNFAIP3 and fatigue were independent risk factors for response to UDCA in PBC patients(P<0.05).The area under the curve for TNFAIP3 and fatigue were 0.691 and 0.704,respectively,while their combination showed a significantly higher area under the curve of 0.848.The expression of TNFAIP3 was also correlated with age,albumin,total bilirubin,alkaline phosphatase and splenomegaly(P<0.05).CONCLUSION TNFAIP3 and fatigue are independent risk factors for response to UDCA in Chinese patients with PBC.TNFAIP3 may be a potential biomarker or therapeutic target for PBC.These findings offer new insights into the pathogenesis of PBC.
基金Supported by the Instituto de Salud Carlos Ⅲ(ISCⅢ)Through the Project Co-Funded by the European Union,No.PI20-00487,No.PI23-00119 and No.PI24-01630.
文摘BACKGROUND Diabetes and its associated microvascular complications,such as nephropathy and retinopathy,significantly impact global health.These complications often begin in the prediabetic stage,emphasizing the importance of early detection and intervention.Inflammatory pathways are key contributors to these conditions,and recent research has identified members of the tumor necrosis factor(TNF)receptor superfamily as potential biomarkers.However,their association with renal and retinal dysfunction in individuals with intermediate hyperglycemia(IH)remains underexplored.The Early Prevention of Diabetes Complications(ePREDICE)trial provides a valuable cohort to investigate these associations and improve risk assessment strategies.AIM To identify inflammatory biomarkers associated with early renal and retinal dysfunction in individuals with IH.Specifically,we evaluate the diagnostic and prognostic potential of TNF receptor superfamily members[TNF receptor 1(TNF-R1),TNF receptor 2(TNF-R2)],T-cell immunoglobulin and mucin domain 3(TIM-3)/HAVCR2,galectin-3,and interleukin-6(IL-6)in detecting kidney dysfunction and retinopathy in this high-risk population.By understanding their roles,we seek to enhance early screening methods and inform personalized intervention strategies.METHODS A cross-sectional analysis of 967 individuals with IH from the ePREDICE trial was conducted.Participants underwent comprehensive anthropometric and biochemical assessments.Key inflammatory biomarkers,including TNF-R1,TNF-R2,TIM-3/HAVCR2,galectin-3,and IL-6,were quantified using immunoassays.Renal function was assessed using estimated glomerular filtration rate(eGFR)and albuminuria,while retinopathy was evaluated through fundoscopic examination.Statistical analyses included adjusted mean comparisons,correlation studies,and receiver operating characteristic curve analysis to assess biomarker diagnostic accuracy.RESULTS TNF-R1,TNF-R2,and TIM-3/HAVCR2 were significantly associated with reduced filtration function(eGFR<60 mL/minute/1.73 m^(2))and albuminuria,with area under the curve(AUC)values between 0.815 and 0.845.TIM-3/HAVCR2 emerged as the strongest predictor of retinopathy(AUC=0.737).Strong correlations(r>0.75)were observed among TNF-R1,TNF-R2,and TIM-3/HAVCR2,suggesting a coordinated role in inflammatory pathways.CONCLUSION Our findings highlight the potential of TNF receptor superfamily members as biomarkers for early-stage renal and retinal complications in individuals with IH.Their integration into clinical screening protocols could facilitate earlier detection,improving patient stratification and personalized management strategies.Further longitudinal studies are necessary to validate their predictive value and potential for guiding therapeutic interventions in IH and early diabetes management.
文摘BACKGROUND Although acute pancreatitis and walled-off necrosis(WON)are rare complications following aortic surgery,they are serious risk factors for postoperative mortality.Considering the poor general condition of the postoperative patient,more effective and less invasive treatments are favorable.CASE SUMMARY A 67-year-old man was referred to our hospital for the treatment of WON after acute pancreatitis.He had undergone total aortic arch replacement due to aortic arch aneurysm and coronary artery bypass grafting due to angina pectoris 6 weeks prior in another hospital.On the second postoperative day,laboratory data and computed tomography showed that the patient had developed acute pancreatitis.Although conservative management(antibiotics,hydration,etc.)had helped in relieving the symptoms of acute pancreatitis,peripancreatic fluid collection(PFC)persisted,accompanied by duodenal obstruction and vomiting.Contrastenhanced computed tomography showed that the heterogeneous enhancement and fluid collection in the pancreatic body and tail had increased,consistent with walled-off WON.We therefore performed endoscopic ultrasound-guided transluminal drainage for the PFC.As a result,the WON resolved gradually,resulting in improved oral intake.CONCLUSION Acute pancreatitis is a rare gastrointestinal complication following thoracic and thoracoabdominal aortic aneurysm surgery.To the best of our knowledge,this is the first case of WON after aortic arch surgery treated with endoscopic ultrasound-guided transluminal drainage for PFC.
基金supported by a grant from the National Natural Science Foundation of China(82470680).
文摘Background:Infected pancreatic necrosis(IPN)is a highly morbid local complication following necrotizing pancreatitis.Early enteral nutrition has been proven to be effective in preventing IPN.This study aimed to assess the association between the trajectory of prealbumin(PAB)during the early phase of acute pancreatitis(AP)and the incidence of IPN and other clinical outcomes.Methods:This retrospective,dual-centered study screened patients with AP admitted to the Center of Acute Pancreatitis,Jinling Hospital and the Affiliated Hospital of Zunyi Medical University from January 2018 to December 2022.The PAB levels during the first week after admission were collected.The primary outcome was the incidence of IPN within 90 days after AP onset.Group-based trajectory modelling was performed to describe the trajectory of PAB levels over time.A Cox proportional hazard model was used to facilitate the interpretation of the time-varying hazard ratio(HR)between PAB and outcomes.Fine-Gray sub-distribution hazard model was adopted for sensitivity analysis.Results:A total of 373 patients were included,of whom 82(22.0%)were diagnosed with IPN within 90 days.The trajectory model assigned 232 patients to the low-level PAB(L-PAB)group and 141 to the high-level PAB(H-PAB)group.The incidence of 90-day IPN in the L-PAB group was significantly higher than that in the H-PAB group(26.7%vs.14.2%,P=0.005).The multivariate Cox regression model showed that a high PAB trajectory was associated with a lower incidence of IPN(HR=0.52,95%CI:0.30-0.89;P=0.017)after adjustment for potential confounders.In the sensitivity analysis,taking death as a com-peting risk,high PAB trajectory remained significantly associated with a lower incidence of IPN in the Fine-Gray model(HR=0.55,95%CI:0.33-0.92;P=0.022).Conclusions:A high PAB trajectory within the first week of AP was significantly associated with a lower incidence of IPN within 90 days after AP onset.Dynamic monitoring of PAB levels in the early phase of AP may play an important role in stratifying patients at high risk of developing IPN.
基金Medical Science and Technology Disciplinary Reserve Talent Program under the Kunming Municipal Health Science and Technology Talent Cultivation Project(Project No.:2024-SW(Reserve)-45)Health Research Project of the Kunming Municipal Health Commission(Project No.:2023-03-06-012)。
文摘Laparoscopic sleeve gastrectomy(LSG),as an effective treatment for morbid obesity and its metabolic complications,exerts its therapeutic effects by significantly reducing body weight and improving metabolic disorders.Its core mechanisms involve multi-level regulation of free fatty acid(FFA)metabolism and chronic low-grade inflammatory states(represented by tumor necrosis factor-alpha,TNF-α).This paper systematically reviews the direct impact of LSG on FFA dynamics including lipolysis,tissue uptake,and oxidation,as well as the molecular pathways through which it indirectly regulates TNF-αby reducing adipose tissue inflammation,improving intestinal barrier function,and modulating epigenetic modifications such as SCD gene methylation.Postoperatively,FFA and TNF-αform a bidirectional promoting feedback loop.LSG effectively breaks this vicious cycle of mutual promotion between the two under obese conditions by reducing FFA levels and inhibiting TNF-αexpression.Lower FFA levels alleviate inflammatory signal activation,while reduced TNF-αinhibits lipolysis,collectively promoting the restoration of insulin sensitivity.A thorough understanding of these mechanisms provides a theoretical basis for optimizing surgical strategies and developing targeted therapies.
文摘In this article,the author comment on the article by Zang et al.Tumor necrosis factor alpha-induced protein 3(TNFAIP3)was examined in this study as a novel biomarker to predict the efficiency of ursodeoxycholic acid(UDCA)and thereby improved primary biliary cholangitis(PBC)treatment.Differentially expressed genes in PBC patients and healthy controls(HCs)were detected using microarray expression analysis.PBC patients and HCs were examined for predictive performance and associations between important genes and clinicopathological features using immunohistochemistry,logistic regression,and receiver operating characteristic curve methods.Thirteen genes linked to the development of PBC were detected by the bioinformatic research.TNFAIP3 was chosen for additional examination from these 13 genes.TNFAIP3 was shown to be more expressed in PBCs patients than in HCs using immunohistochemical method.TNFAIP3 and fatigue have a significant impact on UDCA in PBC patients in multivariate cox regression analysis.Additionally,there was a correlation between TNFAIP3 expression and splenomegaly,alkaline phosphatase,albumin,total bilirubin,and age.In conclusion,TNFAIP3 and fatigue have significant impact on UDCA in PBC.These findings provide a new view on PBC pathophysiology and suggest that TNFAIP3 may be a suitable biomarker or therapeutic target for the disease.
基金Supported by Ministry of Science and Technology,Taiwan,No.MOST 111-2314-B-002-226Taiwan University Hospital,Hsin-Chu Branch,No.112-BIH017The Liver Disease Prevention and Treatment Research Foundation,Taiwan.
文摘BACKGROUND Anti-drug antibodies(ADAs)can reduce the effectiveness of biologics.While human leukocyte antigen(HLA)-DQA1*05 allele is linked to ADA formation in European Crohn’s disease patients,its relevance in non-European populations remains unclear.AIM To investigate HLA genotypes associated with the development of ADAs in Taiwan Region of China inflammatory bowel disease(IBD)patients treated with biologics.METHODS In this multicenter study,IBD patients treated with anti-tumor necrosis factor(TNF),anti-integrin,or anti-interleukin(IL)-12/23 therapies from April 2022 to June 2024 were enrolled.All participants underwent next-generation sequencing for HLA genotyping.ADA levels were measured via enzyme linked immunosorbent assay.HLA allele frequencies were compared between ADA-positive and ADA-negative groups,and against general Taiwan Region of China population data.RESULTS Ninety-five IBD patients were included:58 received anti-TNF therapy(38 infliximab,20 adalimumab),27 antiintegrin,and 10 anti-IL-12/23.ADAs occurred only in the anti-TNF group(n=22):19 infliximab(50%)and 3 adalimumab(15%).No ADAs developed in patients on anti-integrin or anti-IL-12/23 agents.HLA-C*03:04:01 was significantly associated with anti-infliximab ADAs(31.6%vs 0%,P=0.02),and HLA-B*15:18:01 with anti-adalimumab ADAs(66.7%vs 0%,P=0.016).HLA-DQA1*05 was not associated with ADA formation.Frequencies of HLA-C*03:04:01(8.4%vs 10.5%)and HLA-B*15:18:01(1.6%vs 0.6%)in IBD patients were comparable to those in the general population.ADA titers were inversely correlated with serum drug levels.CONCLUSION In Taiwan Region of China IBD patients,HLA-C*03:04:01 and HLA-B*15:18:01 were significantly associated with ADA development to infliximab and adalimumab,respectively.HLA-DQA1*05 was not predictive,highlighting ethnic differences in genetic predisposition to immunogenicity.
基金Supported by The Project of Nantong City Health Committee,No.MS2023027 and WKZL2018017The“333”Talent Funding Project of Jiangsu Province,No.BRA2020198+1 种基金The Project of Jiangsu Provincial Health Commission,No.ZD2021059The Youth Research Fund of Nantong Municipal Health Commission,No.QNZ2023027.
文摘BACKGROUND Irreversible transmural intestinal necrosis(ITIN)is associated with high mortality rates in patients with acute occlusive mesenteric ischemia(AOMI).Currently,there are not many studies on the use of dual energy computed tomography(DECT)for evaluating ITIN.AIM To evaluate the diagnostic value of DECT for ITIN in AOMI.METHODS The cases and computed tomography(CT)images of 102 patients with clinically diagnosed AOMI(including 48 ITIN)from January 2012 to January 2022 were retrospectively collected.The CT scans included both multidetector CT and DECT.The raw data from DECT portal-venous phase were reconstructed into 120 kVp mixed energy image,50 keV virtual monoenergetic imaging,and iodine map.Two radiologists independently completed the subjective visual assessment of CT signs related to AOMI.Objective parameters,including the attenuation of the normal and_(lesion)intestinal wall segment(CT50 keV_(lesion),CT_(50 keV normal/lesion))and iodine concentrations(IC_(lesion)and I_(Cnormal/lesion)),were quantified.Furthermore,multivariate logistic regression,receiver operating characteristic curves,and area under the curve(AUC)values were used to evaluate the subjective and objective indicators in predicting ITIN.RESULTS Regarding subjective signs,logistic regression analysis revealed reduced or absent bowel wall enhancement[odds ratio(OR)=5.576,95%confidence interval(CI):1.547-20.093],bowel dilation(OR=11.613,95%CI:3.790-35.586),and parenchymatous organ infarction(OR=4.727,95%CI:1.536-14.551)were independent risk factors for the ITIN.CT subjective signs had a high diagnostic efficacy for ITIN(AUC=0.853).The two DECT objective parameters also exhibited excellent diagnostic value for ITIN,with an AUC of 0.79,a cut-off value of CT50 keV normal/_(lesion)=2.81,and an AUC of 0.777 with a cut-off value of I_(Cnormal/lesion)=2.39.The Delong test showed that there was no significant difference in the efficacy of subjective CT signs and objective DECT parameters(P>0.05).Importantly,we observed that I_(Cnormal/lesion)combined with subjective signs(bowel dilation and parenchymatous organ infarction)had the highest predictive performance(AUC=0.894),sensitivity(100%),and specificity(70.83%),which was statistically different from the AUC of CT subjective signs(P=0.017).CONCLUSION I_(Cnormal/lesion)(DECT-based features)combined with CT subjective signs(bowel dilatation and parenchymatous organ infarction)showed favorable predictive performance for ITIN in AOMI,which may help clinicians develop timely treatment strategies.
基金Supported by the National Natural Science Foundation of China,No.82260944the Key Research and Development Programs of Guangxi,No.2021AB09011。
文摘BACKGROUND Steroid-induced avascular necrosis of the femoral head(SANFH)involves bone metabolism imbalance and lacks effective therapies.Mesenchymal stem cells(MSCs),particularly human umbilical cord MSCs(hUCMSCs),offer promise due to their osteogenic and immunomodulatory potential.Sclerostin(SOST)inhibits bone formation,so we developed a multi-target gene silencing strategy against SOST using RNA interference.We created hUCMSCs with SOST-silenced(sh-hUCMSCs)and compared their therapeutic efficacy with unmodified hUCMSCs in SANFH mice.This study explores a novel approach to enhance osteogenesis and mitigate SANFH progression.AIM To assess the effects of sh-hUCMSCs on bone metabolism in SANFH.METHODS hUCMSCs were isolated from placental tissue and transfected with SOST-targeting short hairpin RNA plasmids.A SANFH mouse model was established through intraperitoneal injection of lipopolysaccharide(20μg/kg)followed by intramuscular methylprednisolone administration(40 mg/kg).Mice were randomized into four experimental groups(n=10/group):Sham control,SANFH(untreated),hUCMSCs-treated,and sh-hUCMSCs-treated.Micro-computed tomography was used to measure bone volume(BV),bone surface area,bone surface/BV ratio,tra-becular number,trabecular thickness,and trabecular separation.Quantification of adipocyte area by hematoxylin and eosin staining.Collagen fiber volume was assessed by Masson’s trichrome staining.Serum levels of osteopro-tegerin(OPG),receptor activator of nuclear factor kappa B(RANK),RANK ligand(RANKL),tartrate-resistant acid phosphatase,and the OPG/RANKL ratio were measured by enzyme-linked immunosorbent assay.The expression levels of alkaline phosphatase,OPG,SOST,β-catenin,peroxisome proliferator-activated receptor gamma,and CCAAT/enhancer-binding protein in bone tissue were determined by western blot analysis.RESULTS hUCMSCs and sh-hUCMSCs exhibited typical fibroblast-like morphology and high expression of MSC surface markers(CD90,CD73,CD105>98%).These cells demonstrated tri-lineage differentiation potential,confirmed by positive Alizarin Red S,Oil Red O,and Alcian Blue staining,and upregulation of lineage-specific genes.After SOST-RNA interference modification,sh-hUCMSCs showed enhanced inhibition of adipogenesis and improved bone formation in a rat model of SANFH.Histological analysis revealed reduced lipid infiltration and empty lacunae in the femoral head of the sh-hUCMSC group.Western blot showed decreased CCAAT/enhancer-binding protein and peroxisome proliferator-activated receptor gamma expression(P<0.05).Masson staining and micro-computed tomography analysis confirmed significantly increased BV,trabecular number,trabecular thickness,and reduced trabecular separation in the sh-hUCMSC group compared to unmodified MSCs and SANFH groups(P<0.05).Serum enzyme-linked immunosorbent assay showed higher OPG and lower RANK,RANKL,and tartrate-resistant acid phosphatase levels in the sh-hUCMSCs group.Western blot further confirmed upregulated alkaline phosphatase,OPG,β-catenin,and downregulated SOST expression in sh-hUCMSCs compared to controls(P<0.05).These results suggest that SOST inhibition enhances the osteogenic potential and therapeutic efficacy of hUCMSCs in SANFH.CONCLUSION sh-hUCMSCs alleviate SANFH by activating the Wnt/β-catenin signaling pathway,thereby promoting osteogenic differentiation and suppressing adipogenesis to restore bone metabolic balance.
基金Supported by the Earmarked Fund for China Agricultural Research System(No.CARS-45-16)the Key Research and Development Plan of Jiangsu Province(No.BE2021369)。
文摘Mass mortality of mandarin fish(Siniperca chuatsi)due to infectious spleen and kidney necrosis virus(ISKNV)infection occurs frequently.Since there are no effective drug treatments available,prevention relies heavily on detection.Effective and rapid on-site detection methods are needed for early diagnosis of ISKNV.In this study,a rapid and simple colloidal gold test strip method,specific for the antibody against major capsid protein(MCP),was developed and systematically evaluated for the detection of ISKNV.The limit of detection of the test strip is a 1꞉100 dilution of a positive standard serum and the antibody level in the fish could be estimated from the depth of color of the test line.The strips were tested against serum samples of cyprinid herpesvirus-2(CyHV-2),grass carp reovirus(GCRV),largemouth bass ranavirus(LMBV),large yellow croaker iridovirus(LYCIV),and spring viremia of carp virus(SVCV),yielding no cross-reactivity.In addition,10 mandarin fish artificially infected with ISKNV were tested using the current industry standard PCR method(SC/T 7211-2011)on their splenorenal tissues.The results from the test strips showed a high degree of concordance with PCR testing,achieving a Kappa value of 0.737.All the results indicated that the colloidal gold test strips prepared in this study could be used as a simple,rapid,and highly sensitive and specific method for ISKNV diagnosis.
文摘BACKGROUND Hepatic ischemia reperfusion(HIR)injury is a major complication affecting various major liver surgeries,including liver transplantation.Aprepitant(APRE),a neurokinin-1 receptor antagonist,is commonly used as an antiemetic to prevent chemotherapy-induced nausea and vomiting.AIM To assess the potential protective effect of APRE against HIR-induced liver injury via targeting the nucleotide-binding oligomerization domain-,leucine-rich repeat-,and pyrin domain-containing receptor 3/interleukin(IL)-1beta signaling pathway.METHODS Six groups of adult male Wistar albino rats were divided as follows:Sham group,Sham/APRE10 group(APRE 10 mg/kg),HIR group,HIR/APRE5 group(APRE 5 mg/kg),HIR/APRE10 group(APRE 10 mg/kg),and HIR/APRE20 group(APRE 20 mg/kg).Serum alanine transaminase,aspartate transaminase,liver malondialdehyde,total antioxidant capacity levels,as well as IL-6,sirtuin 1(Sirt1),caspase-3,cleaved caspase-3,and tumor necrosis factor alpha biomarkers,were evaluated.Hepatic specimens were examined histopathologically and immunohistochemically for nuclear factor erythroid-2-related factor 2(Nrf2)immunoexpression.RESULTS HIR resulted in hepatic damage,as evidenced by histopathological changes and a significant increase in serum alanine transaminase,aspartate transaminase,hepatic malondialdehyde,caspase-3,and tumor necrosis factor alpha levels.Additionally,there were significant increases in hepatic total antioxidant capacity and reductions in IL-6 and cleaved caspase-3 protein levels,as demonstrated by Western blot analysis,along with enhanced immunoexpression of Sirt1 and Nrf2.APRE has significantly reduced various parameters of oxidative stress,inflammation,and apoptosis,and a significant increase in liver Nrf2 immunoexpression,leading to a significant improvement in the histopathological changes.CONCLUSION In conclusion,targeting the Sirt1/Nrf2 signaling pathway,as demonstrated by APRE in our model,could present a promising therapeutic target to protect against HIR-induced liver injury during major liver surgeries.
基金supported by the Natural Science Foundation of China(81873325)the State Administration of Traditional Chinese Medicine of Zhejiang Province(2021ZZ014).
文摘The study aimed to explore the efficacy and potential mechanisms of a naturally aromatic cyanogenic compound amygdalin(AMY)in treating glucocorticoid(GC)-associated necrosis of the femoral head(GANFH).We demonstrated that GC exacerbates the oxidative stress(OS)microenvironment via promoting nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)expression in human,rat,and mesenchymal stem cells(MSCs)samples,thus generating excessive reactive oxygen species(ROS),leading to increased apoptosis and unbalanced osteolipogenic differentiation.Furthermore,computational docking results revealed that AMY could bind specifically to the predicted binding sites of NOX4.Additionally,AMY ameliorated the OS microenvironment of MSCs via decreasing NOX4 expression and inhibiting NOX4/ROS/p38MAPK signaling,thereby reversing the GC-induced apoptosis and imbalanced osteolipogenic differentiation,and ultimately alleviating GANFH.In summary,we demonstrated for the first time that AMY attenuated apoptosis and maintained osteolipogenic differentiation balance in MSCs via specifically targeting NOX4,inhibiting NOX4/ROS/p38MAPK signaling,thereby treating GANFH.
文摘Objective:To analyze the value of prophylactic antibiotic use in reducing the incidence of pancreatic necrosis in patients with emergency acute pancreatitis(AP).Methods:A total of 70 AP patients who sought medical attention from January 2024 to January 2025 were randomly divided into groups by drawing lots.Group A received prophylactic antibiotic intervention,while Group B received conventional intervention.Results:Group A demonstrated superior outcomes compared to Group B in terms of therapeutic efficacy,duration of symptoms,inflammatory factors,symptom scores,and complication rates,with p<0.05.Conclusion:Prophylactic antibiotic treatment in emergency AP patients leads to a decrease in inflammatory factor levels,alleviation of symptoms,a reduction in the incidence of infectious pancreatic necrosis,and is safe and effective.
基金Research Support Foundation of the State of São Paulo(FAPESP,Brazil),No.2014/25927-2,No.2018/07862-1National Council for Scientific and Technological Development(CNPq,Brazil)Higher Education Personnel Improvement Coordination(CAPES,Brazil).
文摘Ulcerative colitis(UC)and Crohn’s disease(CD)are part of Inflammatory Bowel Diseases(IBD)and have pathophysiological processes such as bowel necrosis and enteric neurons and enteric glial cells.In addition,the main inflammatory mediator is related to the tumor necrosis factor-alpha(TNF-α).TNF-αis a mediator of the intestinal inflammatory processes,thus being one of the main cytokines involved in the pathogenesis of IBD,however,its levels,when measured,are present in the serum of patients with IBD.In addition,TNF-αplays an important role in promoting inflammation,such as the production of interleukins(IL),for instance IL-1βand IL-6.There are two receptors for TNF as following:The tumor necrosis factor 1 receptor(TNFR1);and the tumor necrosis factor 2 receptor(TNFR2).They are involved in the pathogenesis of IBD and their receptors have been detected in IBD and their expression is correlated with disease activity.The soluble TNF form binds to the TNFR1 receptor with,and its activation results in a signaling cascade effects such as apoptosis,cell proliferation and cytokine secretion.In contrast,the transmembrane TNF form can bind both to TNFR1 and TNFR2.Recent studies have suggested that TNF-αis one of the main pro-inflammatory cytokines involved in the pathogenesis of IBD,since TNF levels are present in the serum of both patients with UC and CD.Intravenous and subcutaneous biologics targeting TNF-αhave revolutionized the treatment of IBD,thus becoming the best available agents to induce and maintain IBD remission.The application of antibodies aimed at neutralizing TNF-αin patients with IBD that induce a satisfactory clinical response in up to 60%of patients,and also induced long-term maintenance of disease remission in most patients.It has been suggested that anti-TNF-αagents inactivate the pro-inflammatory cytokine TNF-αby direct neutralization,i.e.,resulting in suppression of inflammation.However,anti-TNF-αantibodies perform more complex functions than a simple blockade.
